Overexpression and proliferation dependence of acyl-CoA thioesterase 11 and 13 in lung adenocarcinoma
Overexpression and proliferation dependence of acyl-CoA thioesterase 11 and 13 in lung adenocarcinoma
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DOI：
10.3892/ol.2017.6594
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发表时间：
2017-09-01
期刊：
影响因子：
2.9
通讯作者：
Hsu, Ya-Ling
中科院分区：
文献类型：
--
作者：
Hung, Jen-Yu;Chiang, Shyh-Ren;Hsu, Ya-Ling
脂肪酰辅酶A（CoA）和代谢酶的代谢产物有助于脂质的生物合成，信号转导和基因转录。以往的研究表明，在肺腺癌患者中观察到血浆中特定游离脂肪酸浓度升高和特定脂肪酰辅酶A代谢酶的过表达。然而，在这个代谢网络中有超过30种酶，并且已经被充分研究。在本研究中，酰基辅酶A合成酶（ACS）和酰基辅酶A硫酯酶（ACOT）家族中的酶的表达水平进行了分析，从基因表达大全收集的六个微阵列表达数据集。肺腺癌组织中ACOT 11和ACOT 13的表达显著高于癌旁肺组织。Kaplan-Meier Kaplan-Mean-Meier Kaplan-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-Mean-短发夹状RNA下调ACOT 11和ACOT 13对肺腺癌细胞株CL 1 -0和CL 1 -5的增殖有抑制作用。虽然ACOT 11和ACOT 13敲除没有显着影响细胞内和培养基游离脂肪酸的总量，ACOT 11和ACOT 13敲除介导的生长抑制被拯救的脂肪酸的添加。总之，ACOT 11和ACOT 13在肺腺癌的临床标本中上调，这可能有助于通过增加脂肪酸的可用性来增加细胞增殖。这两种酶的代谢产物可能对肺腺癌的发展至关重要。
The metabolites of fatty acyl-Coenzyme A (CoA) and metabolic enzymes contribute to lipid biosynthesis, signal transduction, and gene transcription. Previous studies have indicated that elevated concentrations of specific free fatty acids in the plasma and overexpression of specific fatty acyl-CoA metabolic enzymes are observed in patients with lung adenocarcinoma. However, there are > 30 enzymes in this metabolic network and have been fully investigated. In the present study, the expression levels of enzymes in the acyl-CoA synthetase (ACS) and acyl-CoA thioesterase (ACOT) families were analyzed from six microarray expression datasets that were collected from Gene Expression Omnibus. Compared with adjacent non-tumor lung tissue, lung adenocarcinoma tissue exhibited significantly higher ACOT11 and ACOT13 expression. Kaplan-Meier plotter database analysis demonstrated that high levels of ACOT11 and ACOT13 were associated with a worse overall survival rate. The proliferation of the lung adenocarcinoma cell lines CL1-0 and CL1-5 was inhibited when ACOT11 and ACOT13 were downregulated by short hairpin RNA. Although ACOT11 and ACOT13 knockdown did not significantly affect the total amount of intracellular and medium-free fatty acids, ACOT11 and ACOT13 knockdown-mediated growth inhibition was rescued by the addition of fatty acids. In conclusion, ACOT11 and ACOT13 were upregulated in clinical specimens of lung adenocarcinoma, which may contribute to increased cell proliferation through the increased availability of fatty acids. The metabolites of the two enzymes may be critical for development of lung adenocarcinoma.